**11. The UK Leicester halted trial**

procedures that have been performed till that date included 2,048 cases, with a technical success of 98.6%. The stroke rate was 3.08%. The 30-day post-procedure mortality rate was 1.37%. The registry was updated in 2003. The total number of stent procedures performed then became 12392 with a technical success rate of 98.9%. Overall, there was TIA rate of 3.07%, minor strokes of 2.14%, major strokes of 1.20%, and procedure-related deaths of 0.64%. There were 6753 cases done without protection and which incurred a 5.29% rate of strokes and procedurerelated deaths. In the 4221 cases with cerebral protection, there was a 2.23% rate of strokes and procedure-related deaths. The rate of neurologic events was 1.2%, 1.3%, and 1.7% at 1, 2, and

In the following years, several registries that were supported by the device industry were reported. These registries included patients who are considered high risk for CEA because one

**Acronym Sponsor Stent Protection device Result; 30-day death/**

BEACH Boston Scientific WallStent Ex filter 5.4% CABERNET Boston Scientific/ Endotex Nex Stent EPI Filter 3.9% ARCHER Guidant AccuLink AccuNet 7.8% MAVErIC Medtronic Exponent PercuSurge 4% PASCAL Medtronic Exponent Any approved 8% SECuRITY Abott Xact Emboshield 7.2%

**stroke/MI rate**

3 years, respectively.[9]

or more of the following features:

**5.** Unstable angina: class III/IV

**7.** Severe pulmonary disease

**10.** Previous CEA

**11.** Age >80 y

**8.** Contralateral carotid occlusion

**9.** Previous radiation to head/neck

**12.** Surgically inaccessible lesions

**Table 3.** Carotid stent industry-supported high-risk registries

**1.** Class-III/IV congestive heart failure

110 Carotid Artery Disease - From Bench to Bedside and Beyond

**2.** Left ventricular ejection fraction<30%

**4.** Recent myocardial infarction (>24 h <30 d)

**6.** Concurrent requirement for coronary revascularization

**3.** Open heart surgery within 6 weeks

The most outstanding negative trial of carotid angioplasty was form Leicester Royal Infirmary. The study consisted of 23 patients with focal carotid territory symptoms and severe ICA stenosis (>70%) who were randomized to either CEA or CAS. However, only 17 had received their allocated treatment before trial suspension. All 10 CEA operations proceeded without complication, but 5 of the 7 (71.4%) patients who underwent CAS had a stroke, 3 of which were disabling at 30 days. The Data Monitoring Committee invoked the stopping rule and the trial was suspended. The investigators and the Ethics Committee subsequently decided that the trial should not be restarted even in an amended format because of problems with informed consent.[12, 13]

The CAVATAS (Carotid and Vertebral Artery Transluminal Angioplasty Study), was the first randomized trial of CEA versus CAS. 504 patients were randomized from 22 centers in between 1992 and 1997. The majority of patients had recently symptomatic lesions. Only 26% of the angioplasty patients received a stent. The rates of major outcome events within 30 days of first treatment did not differ significantly between endovascular treatment and surgery (6.4% vs. 5.9%, respectively, for disabling stroke or death; 10.0% vs. 9.9% for any stroke lasting more than 7 days, or death). (Figure 21) At 1 year after treatment, restenosis was more usual after endovascular treatment (14%vs. 4%, p<0.001). Complications of cranial nerve injury and myocardial ischemia were only reported in the surgical group. The trial described rates of death and disabling stroke after 3 years of 14.3% in the endovascular group and 14.2% in the surgical group.[14]

Crawley et al compared cerebral hemodynamics and microembolization during CAS versus CEA using TCD. The period during which the ICA was occluded by PTA balloon or by clamp during CEA was timed. Ischemic time was defined as the period during which mean MCA velocity fell to a third or less of baseline. CEA resulted in significantly longer occlusion time and ischemic time than PTA. There were significantly more microembolic signals during PTA than during CEA. There was no correlation between any of the parameters measured and periprocedural stroke.[15]

The SAPPHIRE trial (Stenting and Angioplasty with Protection in Patients at High Risk for Endarterectomy) randomized patients with co-morbid conditions that represented exclusion criteria from the previous major randomized trials of CEA. The rationale was that patients with these co-morbid conditions appear to represent the majority of patients undergoing CEA, and concerns have been raised about the generalizability of the CEA trial results in view of the exclusion of those patients in major CEA trials. SAPPHIRE was designed to test "noninferiority" of CAS versus CEA in the high-risk population with >50% symptomatic or >80% asymptomatic stenosis.[16, 17]

**13. The CARESS trial**

not come in favor of carotid stenting.

endarterectomy for the periprocedural complication rate.[20]

versus 4 6% (p=0 0007), respectively.[21]

**15. EVA-3S**

**14. SPACE**

Carotid REvascularization with Stenting Systems was a prospective, multicenter non-random‐ ized industry-sponsored trial compared standard CEA to carotid stenting in patients with symptomatic (≥50%) and asymptomatic (≥75%) carotid stenosis. There was no significant difference in the 30-day combined all-cause mortality and stroke rate between CEA (2%) and CAS (2%). There was no significant difference in the secondary endpoint of combined 30-day

Update on Carotid Revascularization: Evidence from Large Clinical Trials

http://dx.doi.org/10.5772/57153

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Following the publication of the SAPPHIRE and the CARESS trials, carotid artery stenting rocketed. There was a general felling that carotid artery stenting will prevail and become the preferred choice for carotid revascularization. However, the following randomized trials did

Stent-protected angioplasty versus carotid endarterectomy in symptomatic patients included 1183 patients with symptomatic carotid-artery stenosis. Patients were randomly assigned within 180 days of transient ischemic attack or moderate stroke (modified Rankin scale score of < or =3) to carotid-artery stenting (n=605) or carotid endarterectomy (n=595). The primary endpoint of this hospital-based study was ipsilateral ischemic stroke or death from time of randomization to 30 days after the procedure. The non-inferiority margin was defined as less than 2.5% on the basis of an expected event rate of 5%. Analyses were on an intention-to-treat basis. The rate of death or ipsilateral ischemic stroke from randomization to 30 days after the procedure was 6.84% with carotid-artery stenting and 6.34% with carotid endarterectomy (absolute difference 0.51%, 90% CI -1.89% to 2.91%). The one-sided p value for non-inferiority is 0.09. SPACE failed to prove non-inferiority of carotid-artery stenting compared with carotid

Lon term data showed that in both the intention-to-treat and per-protocol analyses the Kaplan-Meier estimates of ipsilateral ischemic strokes up to 2 years after the procedure and any periprocedural stroke or death do not differ between the carotid artery stenting and the carotid endarterectomy groups (intention to treat 9 5% vs. 8 8%; hazard ratio (HR) 1 10, 95%CI 0 75 to 1 61; log-rank p=0 62; per protocol 9 4% vs. 7 8%; HR 1 23, 95%CI 0 82 to 1 83; log-rank p=0 31). In both the intention-to-treat and per-protocol populations, recurrent stenosis of 70% or more is significantly more frequent in the carotid artery stenting group compared with the carotid endarterectomy group, with a life-table estimate of 10 7% versus 4 6% (p=0 0009) and 11 1%

262 patients were randomly assigned to endarterectomy and 265 to stenting. The cumulative probability of periprocedural stroke or death and non-procedural ipsilateral stroke after 4

all-cause mortality, stroke, and myocardial infarction between CEA and CAS.[19]

All carotid stenting procedures were done with the Angioguard protection device. The trial was conducted at 29 US centers which all had mean complication rate less than 3% for CEA and 4% for CAS. All patients were seen by a team made up of a neurologist, a surgeon, and an interventionist. If the surgeon felt that he or she could not operate, and the interventionist felt that intervention was possible, the patient was entered into a stent registry. Conversely, if the interventionist did not feel that he or she could perform the intervention, and the surgeon felt that surgery was possible, the patient was entered into a surgical registry. 723 patients were enrolled initially. Consensus was achieved in 307 patients who were randomized to either stenting (n = 156) or CEA (n = 151). The stent registry consisted of 409 patients, and the surgical registry included seven. Individual endpoints of death, stroke, and MI at 30 days were lower in patients randomized to stenting. The combined endpoint of death/stroke/MI was statisti‐ cally significantly lower in patients randomized to stenting vs. CEA. The death, stroke or myocardial infarction rate was 11.9% in the CAS group and 19.9 % in the CEA group after 1 year. The SAPPHIRE results indicated that CAS has become a promising alternative to CEA, at least "not inferior".
